Increased Anti‐Psoriatic Effect of Anti‐Inflammatory Dendrimers Using Fluid Catanionic Vesicle‐Based Topical Formulations

Psoriasis is a chronic inflammatory skin disease requiring effective anti-inflammatory treatments. The IMD-006 dendrimer exhibits promising immunomodulatory effects, but optimized formulations are needed to improve skin penetration. This study describes fluid vesicle formulations to enhance IMD-006 delivery and evaluates their anti-psoriatic efficacy in a murine model, offering potential for innovative topical therapies. Due to IMD-006's hydrolytic instability at pH 7, more stable analogues, IMD-036 and IMD-046, are designed with phosphoramidate and triazine branching points, improving hydrolytic resistance. Fluorescent derivatives are also synthesized using copper-free click chemistry for biological studies. These dendrimers are actively internalized by monocytes, promoting an anti-inflammatory phenotype. Encapsulation in highly fluid TriCat catanionic vesicles significantly enhances cellular uptake and skin penetration, particularly for IMD-006 and IMD-036, facilitating deeper tissue diffusion without systemic exposure. A xanthan-based hydrogel incorporating TriCat vesicles loaded with these dendrimers is developed for topical application, improving stability, sustained drug release, and skin permeability. In a psoriatic mouse model, TriCat/IMD-006 and TriCat/IMD-036 formulations significantly reduced disease severity ( p < 0.0001 and p < 0.05 respectively), producing clinical and histopathological outcomes equivalent to corticosteroid treatment. These findings highlight the potential of dendrimer-based formulations as effective topical treatments for psoriasis, offering an alternative to conventional corticosteroids.